We propose to use measures of neural synchrony in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of the neural circuitry underlying visual perception in schizophrenia. Schizophrenia has been conceptualized as a failure of the integration of cognitive and neural processes, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. A growing number of studies have reported that individuals with schizophrenia demonstrate abnormal synchronization in the gamma (3) band of the EEG (30-100 Hz). These 3 oscillations have been proposed to mediate perceptual and cognitive processes by dynamically linking together neurons into functional groups, and are known to critically rely upon the same types of inhibitory interneurons as are disturbed in schizophrenia. Therefore, abnormalities in 3 oscillations in schizophrenia patients may reflect neural circuit abnormalities at the core of this disorder. In previous work we have found that a particular 3 oscillation, the response-locked oscillation (RLO), is sensitive to core symptoms of schizophrenia. In healthy individuals, 3-band RLOs over distinct areas of visual cortex are elicited by objects formed by both real and illusory contours, while an RLO over the prefrontal cortex is elicited by both types of objects. In chronic schizophrenia patients, the occipital RLO elicited by illusory objects exhibits 2 abnormalities: 1) the frequency is reduced from the 3 to the beta (2) band (13-30 Hz);and 2) the degree of phase-locking of this oscillation is positively correlated with thought disorder and disorganization symptom measures, as well as visual hallucinations. These findings converge with psychophysical studies of Gestalt perception, which have found that abnormalities of perceptual integration in schizophrenia-spectrum disorders are related to disorganization and thought disorder. Furthermore, other studies of 3 oscillations in schizophrenia have also found positive correlations between hallucination symptoms and 3 phase synchrony. These findings lead to 2 hypotheses: 1) the occipital RLO reflects a synchrony-based mechanism that is closely involved in perceptual feature-binding, and is sensitive to both primary neural circuitry abnormalities and core symptoms in schizophrenia;and 2) the positive correlations between RLO phase locking and positive symptoms reflect a propensity for neural circuits to synchronize inappropriately in schizophrenia. This project will test these hypotheses in a series of experiments examining chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). Our specific aims are to: 1) extend the findings of RLO abnormalities to a broader range of Gestalt processes;2) investigate the basis of the neural circuit abnormality that causes the RLO to occur at a lower frequency in SZ than HC;3) connect the behavioral abnormalities of Gestalt perception that are associated with disorganization symptomatology and the occipital RLO, which shows correlations with disorganization symptoms. PUBLIC HEALTH RELEVANCE: Schizophrenia affects approximately 1% of the general population and has profound negative consequences for the personal, psychological, and fiscal well being of patients, their families, and society as a whole. This disorder characterizes a major group of patients in the VHA, where the chronically mentally ill (primarily patients with schizophrenia) account for a large proportion of VA mental healthcare costs. To treat and ultimately prevent schizophrenia, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia.